U.S. patent number 7,058,455 [Application Number 10/742,584] was granted by the patent office on 2006-06-06 for interface for making spatially resolved electrical contact to neural cells in a biological neural network.
This patent grant is currently assigned to The Board of Trustees of the Leland Stanford Junior University. Invention is credited to Harvey A. Fishman, Philip Huie, Jr., Daniel V. Palanker, Alexander Vankov.
United States Patent |
7,058,455 |
Huie, Jr. , et al. |
June 6, 2006 |
Interface for making spatially resolved electrical contact to
neural cells in a biological neural network
Abstract
An interface for selective excitation or sensing of neural cells
in a biological neural network is provided. The interface includes
a membrane with a number of channels passing through the membrane.
Each channel has at least one electrode within it. Neural cells in
the biological neural network grow or migrate into the channels,
thereby coming into close proximity to the electrodes. Once one or
more neural cells have grown or migrated into a channel, a voltage
applied to the electrode within the channel selectively excites the
neural cell (or cells) in that channel. The excitation of these
neural cell(s) will then transmit throughout the neural network
(i.e. cells and axons) that is associated with the neural cell(s)
stimulated in the channel.
Inventors: |
Huie, Jr.; Philip (Cupertino,
CA), Palanker; Daniel V. (Sunnyvale, CA), Fishman; Harvey
A. (Menlo Park, CA), Vankov; Alexander (Mountain View,
CA) |
Assignee: |
The Board of Trustees of the Leland
Stanford Junior University (Palo Alto, CA)
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Family
ID: |
32913026 |
Appl.
No.: |
10/742,584 |
Filed: |
December 19, 2003 |
Prior Publication Data
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Document
Identifier |
Publication Date |
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US 20040230270 A1 |
Nov 18, 2004 |
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Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
Issue Date |
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60447796 |
Feb 14, 2003 |
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60447421 |
Feb 14, 2003 |
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Current U.S.
Class: |
607/116;
607/53 |
Current CPC
Class: |
A61B
5/24 (20210101); A61N 1/0543 (20130101); A61B
5/291 (20210101); A61N 1/36046 (20130101) |
Current International
Class: |
A61N
1/05 (20060101) |
Field of
Search: |
;607/53,54,116
;623/6.63 |
References Cited
[Referenced By]
U.S. Patent Documents
Other References
Stephen A. Boppart et al., "A Flexible Perforated Microelectrode
Array for Extended Neural Recordings," IEEE Transactions on
Biomedical Engineering, vol. 39, No. 1, Jan. 1992. cited by other
.
Lars Wallman et al., "Perforated Silicon Nerve Chips with Doped
Registration Electrodes: in Vitro Performance and in Vivo
Operation," IEEE Transactions on Biomedical Engineering, vol. 46,
No. 9, Sep. 1999. cited by other .
Kovacs et al., "Regeneration Microelectrode Array for Peripheral
Nerve Recording and Stimulation," IEEE Transactions on Biomedical
Engineering, vol. 39, No. 9, pp. 893-902 Sep. 1992. cited by other
.
Wallman et al., "Perforated Silicon Nerve Chips with Doped
Registration Electrodes: in Vitro Performance and in Vivo
Operation," IEEE Transactions on Biomedical Engineering, vol. 46
No. 9 pp. 1065-1073 Sep. 1999. cited by other .
Boppart et al., "A Flexible Perforated Microelectrode Array for
Extended Neural Recordings," IEEE Transactions on Biomedical
Engineering, vol. 39, No. 1, pp. 37-42, Jan. 1992. cited by other
.
Huie et al., "Perforated Membrane as an Interface for Focal
Electrical Stimulation of Retina," Investigative Ophthalmology
& Visual Science 2003; 44: E-Abstract 5055. cited by other
.
Huie et al., "Tissue-engineered Neurite Conduits to Connect Retinal
Ganglion Cells to an Electronic Retinal Prosthesis," Investigative
Ophthalmology & Visual Science 2002; 43: E-Abstract 4475. cited
by other.
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Primary Examiner: Manuel; George
Assistant Examiner: Faulcon, Jr.; Lenwood
Attorney, Agent or Firm: Lumen Intellectual Property
Services, Inc.
Government Interests
GOVERNMENT SPONSORSHIP
This invention was made with US Government support under contract
FA8750-04-C-0043 from the Air Force Research Lab. The Government
has certain rights in this invention.
Parent Case Text
CROSS REFERENCE TO RELATED APPLICATIONS
This application claims priority from U.S. provisional applications
60/447,796 and 60/447,421, both filed on Feb. 14, 2003, and both
hereby incorporated by reference.
Claims
What is claimed is:
1. An interface for selectively making electrical contact to a
plurality of neural cells in a biological neural network, said
interface comprising: a) a membrane comprising a first and a second
side having a thickness of less than 0.5 mm and including a
plurality of channels passing through said thickness of said
membrane, said membrane adapted to be disposed in proximity to said
biological neural network, whereby said neural cells are capable of
migrating into said channels; and b) a plurality of first
electrodes disposed within said channels, wherein said channels
including said electrodes are open; wherein sufficient space is
present in said channels to permit migration of at least one of
said neural cells to pass from said first side of the membrane
toward the other said second side of the membrane through said
channels.
2. The interface of claim 1, wherein said membrane thickness is in
a range from about 5 microns to about 100 microns.
3. The interface of claim 1, wherein said first electrodes are in
physical contact with said neural cells.
4. The interface of claim 1, wherein said first electrodes are
spaced apart from said neural cells.
5. The interface of claim 1, wherein said biological neural network
comprises a brain cortex neural network.
6. The interface of claim 1, wherein said biological neural network
comprises a retinal neural network.
7. The interface of claim 6, wherein said membrane is disposed
subretinally.
8. The interface of claim 1, wherein said first electrodes are
connected to a plurality of photo-sensitive circuits.
9. The interface of claim 1, wherein said first electrodes are
coated with a high surface area layer, whereby electrochemical
erosion of said electrodes is substantially reduced.
10. The interface of claim 1, further comprising i) a plurality of
wires connected to said first electrodes and disposed on a surface
of said membrane, and ii) an insulating layer disposed on said
surface and covering said wires.
11. The interface of claim 1, further comprising a stop layer
disposed on a surface of said membrane facing away from said
biological neural network, whereby cellular migration past said
stop layer is substantially prevented.
12. The interface of claim 11, wherein said stop layer comprises
pores overlapping with said channels, said pores being smaller than
said channels.
13. The interface of claim 11, wherein said stop layer is permeable
to nutrient flow.
14. The interface of claim 1, wherein said plurality of channels is
arranged in a two-dimensional array.
15. The interface of claim 1, wherein each of said channels is
substantially circular.
16. The interface of claim 15, wherein each of said channels has
substantially uniform diameter along its length, and wherein said
diameter is in a range from about 5 microns to about 50
microns.
17. The interface of claim 15, wherein said membrane comprises a
first layer facing said biological neural network, and a second
layer facing away from said biological neural network, and wherein
each of said channels has a larger diameter in said second layer
than in said first layer.
18. The interface of claim 17, wherein said first electrodes are
disposed on a surface of said first layer facing said second
layer.
19. The interface of claim 17, wherein said first layer comprises a
semiconductor layer.
20. The interface of claim 17, wherein said first layer comprises a
plurality of photo-sensitive circuits connected to said
electrodes.
21. The interface of claim 17, further comprising a second
electrode disposed on a surface of said first layer facing said
biological neural network.
22. The interface of claim 21, wherein said second electrode is
common to all of said plurality of channels.
23. The interface of claim 21, wherein said second electrode is
transparent.
24. The interface of claim 17, further comprising a stop layer
affixed to a surface of said second layer facing away from said
first layer, whereby cellular migration past said stop layer is
substantially prevented.
25. The interface of claim 24, wherein said stop layer comprises
pores overlapping with said channels, said pores being smaller than
said channels.
26. The interface of claim 24, wherein said stop layer is permeable
to nutrient flow.
27. The interface of claim 17, further comprising an intermediate
layer disposed in between said first and second layers, wherein
said channels have a smaller diameter within said intermediate
layer than within said first layer.
28. The interface of claim 27, wherein said electrode is disposed
on a surface of said intermediate layer facing said second
layer.
29. A method for selectively making electrical contact to a
plurality of neural cells in a biological neural network, said
method comprising: a) positioning a membrane in proximity to said
biological neural network, said membrane having a first and a
second side, a thickness of less than 0.5 mm and including a
plurality of channels passing through said thickness of said
membrane, whereby said neural cells are capable of migrating into
said channels; and b) providing a plurality of electrodes disposed
within said channels, wherein said channels including said
electrodes are open; wherein sufficient space is present in said
channels to permit migration of a least one of said neural cells to
pass from said first side of the membrane toward the other said
second side of the membrane through said channels.
30. The method of claim 29, further comprising allowing at least
one of said neural cells to migrate into at least one of said
channels.
31. The method of claim 29, further comprising inducing at least
one of said neural cells to migrate into at least one of said
channels.
Description
FIELD OF THE INVENTION
The present invention relates generally to electrical stimulation
or sensing of neural cells. More particularly, the present
invention relates to an electrode configuration for selectively
making electrical contact to neural cells.
BACKGROUND
Several degenerative retinal diseases that commonly lead to
blindness, such as retinitis pigmentosa and age-related macular
degeneration, are primarily caused by degradation of photoreceptors
(i.e., rods and cones) within the retina, while other parts of the
retina, such as bipolar cells and ganglion cells, remain largely
functional.
Accordingly, an approach for treating blindness caused by such
conditions that has been under investigation for some time is
provision of a retinal prosthesis connected to functional parts of
the retina and providing photoreceptor functionality.
Connection of a retinal prosthesis to functional parts of the
retinal is typically accomplished with an array of electrodes (see,
e.g., U.S. Pat. No. 4,628,933 to Michelson). Michelson teaches a
regular array of bare electrodes in a "bed of nails" configuration,
and also teaches a regular array of coaxial electrodes to reduce
crosstalk between electrodes. Although the electrodes of Michelson
can be positioned in close proximity to retinal cells to be
stimulated, the electrode configurations of Michelson are not
minimally invasive, and damage to functional parts of the retina
may be difficult to avoid.
Alternatively, a prosthesis having electrodes can be positioned
epiretinally (i.e., between the retina and the vitreous humor)
without penetrating the retinal internal limiting membrane (see,
e.g., U.S. Pat. No. 5,109,844 to de Juan et al.). Although the
arrangement of de Juan et al. is less invasive than the approach of
Michelson, the separation between the electrodes of de Juan et al.
and retinal cells to be stimulated is larger than in the approach
of Michelson.
Such increased separation between electrodes and cells is
undesirable, since electrode crosstalk and power required to
stimulate cells both increase as the separation between electrodes
and cells increases. Furthermore, increased electrical power has
further undesirable effects such as increased resistive heating in
biological tissue and increased electrochemical activity at the
electrodes.
U.S. Pat. No. 3,955,560 to Stein et al. is an example of an
approach which provides low separation between electrodes and nerve
fibers (i.e., axons), but requires a highly invasive procedure
where a nerve is cut and then axons regenerate through a prosthesis
and past electrodes embedded within the prosthesis.
OBJECTS AND ADVANTAGES
Accordingly, an objective of the present invention is to provide
apparatus and method for selectively making electrical contact to
neural cells with electrodes in close proximity to the cells and in
a minimally invasive manner.
Another objective of the present invention is to instigate or allow
migration of the neural cells towards the stimulating electrodes in
order to minimize the distance between an electrode and a cell.
Yet another objective of the present invention is to preserve
functionality of a biological neural network when instigating or
allowing migration of neural cells.
Still another objective of the present invention is to reduce
cross-talk between neighboring electrodes.
Another objective of the present invention is to ensure low
threshold voltage and current for cell excitation.
Yet another objective of the present invention is to provide an
interface that allows for mechanical anchoring of neural tissue to
a prosthesis.
Still another objective of the present invention is to provide a
large electrode surface area to decrease current density and
thereby decrease the rate of electrochemical erosion.
An advantage of the present invention is that a selected cell or
group of neural cells can be brought into proximity to stimulating
or sensing electrodes while preserving the signal processing
functionality of a biological neural network. A further advantage
of the present invention is that by bringing cells into close
proximity to electrodes, electrical power required for cell
excitation is reduced, thus decreasing tissue heating and electrode
erosion. Another advantage of the present invention is that close
proximity between cells and electrodes reduces cross-talk with
non-selected cells, thus allowing a higher packing density of
electrodes which provides improved spatial resolution.
SUMMARY
The present invention provides an interface for selective
excitation or sensing of neural cells in a biological neural
network. The interface includes a membrane with a number of
channels passing through the membrane. Each channel has at least
one electrode within it. Neural cells in the biological neural
network grow or migrate into the channels, thereby coming into
close proximity to the electrodes.
Once one or more neural cells have grown or migrated into a
channel, a voltage applied to the electrode within the channel
selectively excites the neural cell (or cells) in that channel. The
excitation of these neural cell(s) will then transmit throughout
the neural network (i.e., cells and axons) that is associated with
the neural cell(s) stimulated in the channel. Alternatively,
excitation of a neural cell (or cells) within the channel due to
activity within the biological neural network is selectively sensed
by the electrode within the channel.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 shows an embodiment of the invention having a membrane with
channels positioned under a retina.
FIG. 2 shows an embodiment of the invention having a membrane with
channels positioned under a retina, and having cells from the inner
nuclear layer migrated into the channels.
FIG. 3 shows a side view of an embodiment of the invention having a
membrane with an electrode exposed inside the channel and coated
outside the channel at the bottom of the membrane.
FIG. 4 shows a bottom view of an embodiment of the invention
according to FIG. 3.
FIG. 5 shows an embodiment of the invention having a membrane with
channels positioned under a retina, and having neural cells
migrated into the channels. Voltage applied to a channel electrode
causes excitation of neural cells in that channel. The excited
neural cells in that channel transmit signal(s) to the retinal
network.
FIG. 6 shows an embodiment of the invention having channels with
two different channel diameters, and having a stop layer at the
bottom to prevent cell migration past the channel while allowing
nutrient flow.
FIG. 7 shows an embodiment of an array according to the present
invention.
FIG. 8 shows an embodiment of the invention where only a few
(ideally one) neural cells can enter the channel. An electric field
is applied across the cell providing efficient stimulation.
FIG. 9 shows an embodiment of the invention having an electrode
and/or an insulator laterally extending into a channel.
FIG. 10 shows an embodiment of the invention having photosensitive
circuitry connected to the electrodes, and having a perforated stop
layer at the bottom to prevent cell migration past the channel
while allowing nutrient flow.
DETAILED DESCRIPTION OF THE DRAWINGS
FIG. 1 shows an embodiment of the invention having a membrane 110
with a plurality of channels 120 passing through membrane 110. In
the example of FIG. 1, membrane 110 is preferably positioned under
a retina 130. Exemplary retina 130 includes photoreceptors (i.e.,
rods and/or cones) 140, inner nuclear layer cells 150 (e.g.,
bipolar cells), ganglion cells 160 and respective axons connecting
to an optic nerve 170. Membrane 110 can be of any type of
biocompatible material that is substantially electrically
non-conductive and is flexible enough to conform to the shape of
the neural tissue in a biological neural network. Suitable
materials for membrane 110 include mylar and PDMS
(polydimethylsiloxane). The thickness of membrane 110 is less than
0.5 mm, and is preferably between about 5 microns and about 100
microns. Channels 120 pass completely through membrane 110 and can
be of any shape, although substantially circular shapes are
preferred. Retina 130 on FIG. 1 is an example of a biological
neural network. The invention is applicable to making electrical
contact to any kind of biological neural network, including but not
limited to: central nervous system (CNS) neural networks (e.g.,
brain cortex), nuclei within the CNS, and nerve ganglia outside the
CNS. A biological neural network is made up of interconnected
biological processing elements (i.e., neurons) which respond in
parallel to a set of input signals given to each.
FIG. 2 shows cell migration into channels 120 of membrane 110 of
FIG. 1. When membrane 110 is positioned near a layer of neural
tissue, neural cells in the neural tissue layer will tend to grow
or migrate towards the channels. This growth process is a natural
physiological response of cells and may depend on the existence of
nutrients, space and a suitable surface morphology for these cells.
Optionally, a growth (or inhibition) factor could be included to
enhance (or decrease) the migration or growth of the neural cells.
Such factors include but are not limited to: BDNF (brain-derived
neurotrophic factor, CNTF (ciliary neurotrophic factor), Forskolin,
Laminin, N-CAM and modified N-CAMs. However, such a growth or
inhibition factor is not always necessary. In the example of FIG.
2, cells 210 are neural cells 150 which have migrated into and/or
through channels 120 in membrane 110 positioned subretinally. The
diameter of each channel should be sufficient to allow migration of
neural cells 150, and is preferably in a range from about 5 microns
to about 20 microns. We have found experimentally that such cell
migration tends to occur easily when membrane 110 is disposed
subretinally (i.e. between the retina and the outer layers of the
eye), and tends not to occur easily (or at all) when membrane 110
is disposed epiretinally (i.e. between the retina and the vitreous
humor). Penetration of neural cells 150 into and through channels
120 provides mechanical anchoring of retina 130 to membrane
110.
FIG. 3 shows an enlarged view of one of the channels of the
configuration of FIG. 2. In the example of FIG. 3, an electrode 310
is positioned inside channel 120 in membrane 110 leaving enough
space for neural cells 210 and their axons to migrate and grow
through the channel. As a result of this cell migration, electrode
310 is in close proximity to neural cells 210. Electrode 310 is
shown extending to a bottom surface of membrane 110 (i.e., a
surface of membrane 110 facing away from the biological neural
network). Wires (not shown) can connect electrodes 310 to input
and/or output terminals (not shown), or to circuitry within
membrane 110. In such cases where electrodes 310 and optionally
wires are present on the bottom surface of membrane 110, a
non-conductive layer 350 is preferably disposed on the bottom
surface of membrane 110 covering electrodes 310 (and any wires, if
present) to provide electrical isolation. FIG. 4 shows a view as
seen looking up at non-conductive layer 350 of two channels 120
having the configuration of FIG. 3. FIG. 4 also shows close
proximity between electrodes 310 and cells 210.
Electrodes 310 are in electrical contact with neural cells 210, but
may or may not be in physical contact with neural cells 210. Direct
physical contact between electrodes 310 and cells 210 is not
necessary for electrodes 310 to stimulate cells 210, or for
electrodes 310 to sense activity of cells 210.
FIG. 5 shows operation of the configuration of FIG. 2. A selected
neural cell (or cells) 510 within one of channels 120 is
electrically excited by an electrode within the same channel.
Impulses from neural cell (or cells) 510 excite selected ganglion
cells 520, which in turn excite selected optic nerve fibers
530.
Many advantages of the present invention are provided by the
configurations discussed in connection with FIGS. 1 5. In
particular, close proximity between electrodes 310 and migrated
cells 210 is provided, which reduces the electrical power required
to stimulate cells 210 and decreases cross-talk to unselected cells
(i.e., cells not within the channel 120 corresponding to a
particular electrode 310). Reduction of electrical power required
to stimulate cells 210 leads to reduced tissue heating and to
reduced electrochemical erosion of electrodes 310. Reduction of
cross-talk to unselected cells provides improved spatial
resolution. Furthermore, electrodes 310 are well insulated from
each other by membrane 110, so electrode to electrode cross-talk is
also reduced. Additionally, the growth and/or migration of neural
cells 150 into channels 120 preserves existing functionality of
retina 130.
However, the configurations shown in FIGS. 1 5 do not directly
limit growth and/or migration of cells through channels 120. In
some cases, we have found that many cells grow or migrate through
channels 120, leading to the formation of significant uncontrolled
"tufts" of cells and/or cell processes facing away from the retina.
Such uncontrolled tuft growth can lead to fusing of adjacent tufts,
which tends to undesirably increase crosstalk. Also, electrodes 310
have a small surface area, which increases current density and thus
increases undesirable electrochemical activity at electrodes
310.
FIG. 6 shows an interface 600 according to an embodiment of the
invention which prevents the formation of such uncontrolled retinal
tufts and provides increased electrode surface area. In the
embodiment of FIG. 6, a first layer 610 and a second layer 630 form
a membrane analogous to membrane 110 of FIG. 1. A channel passes
through both first layer 610 and second layer 630, where the
channel diameter d2 in second layer 630 is larger than the channel
diameter d1 in first layer 610. The thickness of layers 610 and 630
together is less than 0.5 mm. The thickness of layer 610 is
preferably between about 10 microns and about 50 microns. The
thickness of layer 630 is preferably between about 5 microns and
about 50 microns. A stop layer 620 is disposed such that second
layer 630 is in between first layer 610 and stop layer 620. Stop
layer 620 is shown as having a hole with diameter d3 aligned to the
channel through layers 610 and 630. An electrode 640 is disposed on
a surface of first layer 610 facing second layer 630.
Layers 610, 620, and 630 can be of any type of biocompatible
material that is substantially electrically non-conductive and is
flexible enough to conform to the shape of the neural tissue in a
biological neural network. Suitable materials include mylar and
PDMS (polydimethylsiloxane).
First layer 610 is in proximity to and faces a biological neural
network (not shown on FIG. 6). Retina 130 as shown on FIG. 1 is an
example of such a biological neural network. As discussed above in
connection with FIG. 2, cells tend to grow or migrate into channels
within layer 610, provided there is sufficient room. Accordingly,
the diameter d1 should be sufficiently large to allow migration of
neural cells (such as 150 on FIG. 1), and is preferably in a range
from about 5 microns to about 50 microns.
The function of stop layer 620 is to prevent uncontrolled growth of
a retinal tuft past stop layer 620, while permitting nutrients to
flow to a cell (or cells) within the channel passing through layers
610 and 630. Therefore, diameter d3 should be small enough to
prevent growth or migration of cells (or cell process) through stop
layer 620. Preferably, d3 is less than about 5 microns in order to
prevent cell migration through stop layer 620. Alternatively, stop
layer 620 can include several small holes each having a diameter of
less than about 5 microns, where the holes in layer 620 are aligned
with the channel within second layer 630. More generally, stop
layer 620 can be either an impermeable membrane having at least one
hole in it large enough to permit nutrient flow and small enough to
prevent cells from moving through it, or a membrane which is
permeable to nutrient flow.
Since diameter d2 is larger than diameter d1, a retinal tuft may
form within the channel through second layer 630. Such retinal tuft
formation is not uncontrolled, since the maximum size of the
retinal tuft is determined by stop layer 620. In fact, controlled
retinal tuft formation is likely to be desirable, since it will
tend to provide improved mechanical anchoring of interface 600 to a
retina.
Electrode 640 is disposed on a surface of first layer 610 facing
second layer 630 and within the channel passing through the two
layers. Since d2 is greater than d1, the surface area of electrode
640 can be made significantly larger than the area of an electrode
within a channel having a uniform channel diameter along its length
(such as shown on FIG. 3). The diameter d2 is preferably from about
10 microns to about 100 microns. In the example of FIG. 6, an
electrode 650 is disposed on the top surface of first layer 610. An
applied voltage between electrodes 640 and 650 provides an electric
field within the channel passing through first layer 610.
One variation of the present invention is to coat electrode 640 to
further increase its surface area and to further decrease the
current density and associated rate of electrochemical erosion of
the conductive layer. For example, carbon black has a surface area
of about 1000 m.sup.2/g and so a coating of carbon black on
electrode 640 can significantly increase its effective surface
area. Other suitable materials for such a coating include platinum
black, iridium oxide, and silver chloride.
Laser processing can be used to form channels. In the case of the
embodiment of FIG. 6, the largest holes (i.e. the channels through
second layer 630) are formed first, then layers 630 and 610 are
attached to each other. The next largest holes are then formed,
using the previously formed holes for alignment, and stop layer 620
is then attached to second layer 630. Finally, the smallest holes
(if necessary) are formed in stop layer 620, using previously
formed holes for alignment. Electrodes 640 on first layer 610 can
also be formed by laser processing. For example, first layer 610
can have a continuous film of metal deposited on the surface of
layer 610 that will eventually face toward second layer 630, and
laser processing of this continuous film of metal can define
electrodes 640 (and optionally wires connected to these electrodes
as discussed in connection with FIG. 3). Laser processing methods
to perform these tasks are known in the art.
FIG. 7 shows an interface 700 including several interfaces 600
(shown as 600a, 600b, 600c, etc.) according to FIG. 6, for making
selective contact to multiple points in a retina. Typically,
interfaces 600 within interface 700 are arranged as a
two-dimensional array, where each channel corresponds to a pixel of
the array. In the embodiment of FIG. 7, electrode 650 is preferably
a common electrode for all channels. Resistance between electrodes
640 corresponding to different array elements is largely determined
by the diameter d3 of the hole in stop layer 620, since conduction
is mainly through extra cellular fluid surrounding interfaces 600.
Accordingly, the selection of d3 (or equivalently, the total open
area in stop layer 620) is determined by a tradeoff between
reducing electrode to electrode cross-talk (by decreasing d3) and
providing sufficient nutrient flow (by increasing d3).
FIG. 8 shows operation of interface 600, where a single cell 820
has migrated into the channel passing through first layer 610. In
practice, several cells may be present in this channel, although
the ideal situation of having only a single cell in the channel is
preferred because it provides maximum selectivity of excitation. A
potential difference between electrodes 640 and 650 creates an
electric field 810 passing through cell 820 as shown. Electric
field 810 depolarizes cell 820 to stimulate it, and the resulting
signal travels into the rest of the retina as indicated in FIG.
5.
FIG. 9 shows operation of an interface 900 which is a variation of
interface 600. In interface 900, electrode 640 and/or an insulating
intermediate layer 920 is/are extended partway into the channel
passing through first layer 610. The example of FIG. 9 shows both
electrode 640 and intermediate layer 920 extending into the
channel. Such reduction of the minimum channel diameter reduces the
electrical power required to excite cell 820, because the impedance
of electrode 640 increases. A part of the cell 820 located close to
the small opening in electrode 640 and intermediate layer 920 will
be depolarized. Extension of electrode 640 in this manner also
further increases its surface area, which desirably reduces the
rate of electrochemical erosion of electrode 640.
FIG. 10 shows operation of an interface 1000 according to another
embodiment of the invention. In the embodiment of FIG. 10, a first
layer 1010 and a second layer 1020 form a membrane analogous to
membrane 110 of FIG. 1. A channel passes through both first layer
1010 and second layer 1020, where the channel diameter in second
layer 1020 is larger than the channel diameter in first layer 1010.
The thickness of layers 1010 and 1020 together is less than 0.5 mm.
As shown on FIG. 10, the thickness of second layer 1020 is on the
order of several times a typical cell dimension, to provide room
for formation of a controlled retinal tuft within second layer
1020. Layer 1010 preferably has a thickness between about 5 microns
and about 50 microns. Layer 1020 preferably has a thickness between
about 5 microns and about 100 microns. A stop layer 1030 is
disposed such that second layer 1020 is in between first layer 1010
and stop layer 1030.
The function of stop layer 1030 is to prevent uncontrolled growth
of a retinal tuft past stop layer 1030, while permitting nutrients
to flow to a cell (or cells) within the channel passing through
layers 1010 and 1020. Stop layer 1030 is shown as having several
small holes aligned to the channel through layer 1020. Preferably,
these holes each have a diameter of less than about 5 microns, to
prevent cell migration through the holes. Alternatively, stop layer
1030 could have a single small hole per channel, as shown on FIG.
6. More generally, stop layer 1030 can be either an impermeable
membrane having at least one hole in it large enough to permit
nutrient flow and small enough to prevent cells from moving through
it, or a membrane which is permeable to nutrient flow.
An electrode 1090 is disposed on a surface of first layer 1010
facing second layer 1020, and another electrode 1080 is disposed on
a surface of first layer 1010 facing away from second layer 1020. A
photo-sensitive circuit 1070 (e.g., a photodiode, a
phototransistor, etc.) is fabricated within first layer 1010 and is
connected to electrodes 1080 and 1090. Electrode 1080 is preferably
transparent to light and/or patterned in such a way that allows for
light penetration to photo-sensitive circuit 1070.
The embodiment of FIG. 10 provides photo-sensitive circuit 1070
connected to electrodes 1080 and 1090. Accordingly, it is
preferable for layer 1010 to be fabricated from a light-sensitive
material permitting fabrication of photo-sensitive circuitry 1070
(e.g., any of various compound semiconductors such as GaAs and the
like). Furthermore, for this embodiment, it is convenient for
layers 1020 and 1030 to be materials compatible with the processing
technology of the material of layer 1010. For example, layers 1020
and 1030 can be polymers (e.g., photoresists) or inorganic
materials (e.g., oxides or nitrides). Channels through layers 1010
and 1020 (and holes through layer 1030) are preferably formed via
lithography, in order to enable rapid fabrication of devices having
a large number of channels. Since the materials indicated above are
not typically bio-compatible, biological passivation of embodiments
of the invention made with such materials is preferred. Suitable
biological passivation techniques for such materials are known in
the art.
In operation of interface 1000, light impinging on photo-sensitive
circuit 1070 leads to generation of a potential difference between
electrodes 1080 and 1090. Optionally, electronic amplification of
the signal of photo-sensitive circuit 1070 is provided by
amplification circuitry (not shown) to increase the signal at
electrodes 1080 and 1090 responsive to illumination of
photo-sensitive circuit 1070. The potential difference between
electrodes 1080 and 1090 provides an electric field 1040 passing
through a cell 1050 within the channel. Excitation of cell 1050 by
electric field 1040 provides selective excitation of the retina, as
shown on FIG. 5.
The present invention has now been described in accordance with
several exemplary embodiments, which are intended to be
illustrative in all aspects, rather than restrictive. Thus, the
present invention is capable of many variations in detailed
implementation, which may be derived from the description contained
herein by a person of ordinary skill in the art.
For example, additional perforations can be included in the
membrane to assist and/or ensure flow of nutrients. The diameter of
such perforations should be smaller than the diameter of the
channels to avoid neural cell migration through these additional
perforations (i.e., tuft formation), but large enough to ensure a
flow of nutrients. Specific growth factor(s) or surface coatings
can be used to ensure migration of a particular cell group, e.g.
only bipolar cells, or even a specific type of bipolar cell (e.g.,
"on" or "off" cells). Also, the interface can have some channels or
perforations for stimulation purposes while other channels or
perforations can be designed for mechanical anchoring to neural
tissue
The present invention is not limited to placement of the interface
under the neural tissue since the interface can also be placed over
or within the neural tissue. The interface can be used as a
prosthetic device to connect to various kinds of neural tissue and
is not limited to a retinal prosthesis or interface.
The interface has been discussed in light of electrically
stimulating a select group of neural cells, however, the interface
could also be used to measure signals generated in neural cells due
to an external trigger/excitation, for example, signals generated
in retinal cells due to light excitation.
In the discussion of FIG. 10, a preferred lithographic fabrication
approach for the embodiment of FIG. 10 was discussed. Likewise,
laser processing was discussed in connection with the embodiment of
FIG. 6. The invention is not limited to any one fabrication method.
Thus the use of lithography is not restricted to the embodiment of
FIG. 10. Similarly, the use of laser processing is not restricted
to the embodiment of FIG. 6.
All such variations are considered to be within the scope and
spirit of the present invention as defined by the following claims
and their legal equivalents.
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